Minority populations are exposed to high levels of trauma and have minimal access to psychiatric and general medical care. The studies proposed in the current application seek to investigate the psychobiological mechanisms responsible for elevated cardiometabolic illness risk in African-American women of lower socioeconomic status (SES) with type 2 diabetes mellitus (T2DM) and trauma-related psychopathology (post- traumatic stress disorder [PTSD] and/or major depressive disorder [MDD]). PTSD in particular, and certain forms of mood and anxiety disorders in general, have been repeatedly associated with dysregulation of the nervous, neuroendocrine, and immune systems that is generally characterized by increased circulating norepinephrine and reduced parasympathetic tone, abnormal secretion of cortisol, and variably elevated systemic inflammation. Quantitative differences in the production of autonomic, neuroendocrine, and inflammatory innate immune mediators of the stress response, distinct from those observed in psychologically healthy subjects, are found in patients with PTSD, MDD, or PTSD/MDD. As a consequence, stress mediators may differentially influence the development and progression of obesity, dyslipidemia, carbohydrate intolerance, and impaired endothelial function in patients affected by PTSD and/or MDD through diagnosis- dependent biological pathways. Although a number of reports suggest a relationship between autonomic, neuroendocrine, and immune factors when attempting to understand the pathophysiological mechanisms linking cardiometabolic illnesses and trauma-related psychiatric disorders, to date no studies have examined in a comprehensive manner the ways by which these systems interact. Accordingly, this project seeks to leverage our extensive experience with a low SES, African-American, primary care population with the well-developed research and recruiting infrastructure of the parent project (MH071537) to test the following three hypotheses in a sample of (N=140) female, African-American primary care patients with T2DM: 1.) Significant differences in measures of autonomic and neuroendocrine function assessed before, during, and after psychosocial stress challenge (Trier Social Stress Test) will be identified between trauma- exposed controls and subjects diagnosed with PTSD, MDD, or PTSD+MDD; 2.) Measurements of autonomic function and neuroendocrine mediators collected before, during, and after psychosocial stress challenge will predict measurements of inflammatory mediators collected before, during, and after the psychosocial stress challenge; 3.) Innate inflammatory mediators collected before, during, and after psychosocial stress challenge will predict differences in standard measures of cardiometabolic function (e.g. glucose tolerance test, flow mediated vasodilatation). Knowledge gained by the experiments proposed in this application will increase our understanding of the psychobiology of stress in women with T2DM and trauma-related psychopathology.